<scp>SMARCA4</scp> and <scp>SMARCE1</scp> in gastric cancer: Correlation with <scp>ARID1A</scp>, and microsatellite stability, and <scp><i>SMARCE1</i></scp>/<scp><i>ERBB2</i></scp> co‐amplification

Pries, Katharina; Krüger, Sandra; Heckl, Stefan; Behrens, Hans‐Michael; Röcken, Christoph

doi:10.1002/cam4.5776

Cited by 5 publications

(1 citation statement)

References 41 publications

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“…The exploration of SMARCA4 mutations in GEA is relatively uncharted in the literature, with few studies addressing their clinicopathological implications [25,26]. Our study contributes to this emerging field by demonstrating a significant association between SMARCA4 mutations and the non-signet ring cell subtype.…”

Section: Discussionmentioning

confidence: 64%

SMARCA4 Mutations in Gastroesophageal Adenocarcinoma: An Observational Study via a Next-Generation Sequencing Panel

Yamashita,

Sewastjanow-Silva,

Yoshimura

et al. 2024

Cancers

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Background: The clinical impact of SMARCA4 mutations (SMARCA4ms) in gastroesophageal adenocarcinoma (GEA) remains underexplored. This study aimed to examine the association of SMARCA4ms with clinical outcomes and co-occurrence with other gene mutations identified through a next-generation sequencing (NGS) panel in GEA patients. Methods: A total of 256 patients with metastatic or recurrent GEA who underwent NGS panel profiling at the MD Anderson Cancer Center between 2016 and 2022 were included. Comparative analyses were performed to assess clinical outcomes related to SMARCA4ms. The frequency and types of SMARCA4ms and their co-occurrence with other gene mutations were also examined. Results: SMARCA4ms were identified in 19 patients (7.4%). These SMARCA4ms were significantly associated with non-signet ring cell subtype (p = 0.044) and PD-L1 positive expression (p = 0.046). No difference in survival between the SMARCA4m and SMARCA4-normal group was observed (p = 0.84). There were significant associations between SMARCA4ms and FANCA, IGF1R, KRAS, FANCL, and PTEN alterations. Notably, 15 of the 19 SMARCA4m cases involved SNV missense mutations, with frequent co-occurrences noted with TP53, KRAS, ARID1A, and ERBB2 mutations. Conclusions: These results serve as the first comprehensive examination of the relationship between SMARCA4ms and clinical outcomes in GEA.

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Section: Discussionmentioning

confidence: 64%

SMARCA4 Mutations in Gastroesophageal Adenocarcinoma: An Observational Study via a Next-Generation Sequencing Panel

Yamashita,

Sewastjanow-Silva,

Yoshimura

et al. 2024

Cancers

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SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response

Zhang,

Sun,

Han

et al. 2024

FEBS Open Bio

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The switch/sucrose non‐fermenting (SWI/SNF) complex family includes important chromatin‐remodeling factors that are frequently mutated in lung adenocarcinoma (LUAD). However, the role of one family member, SMARCA4, in LUAD prognosis and immunotherapy sensitivity remains unclear. In the present study, 6745 LUAD samples from the cBioPortal database were used to analyze the relationships between SMARCA4 mutations and patient prognoses and clinical characteristics. Additionally, we examined the correlation between SMARCA4 mutations and prognosis in patients treated with immunotherapy using two immune‐related datasets. SMARCA4 mutations and low expression were associated with shorter survival, and mutations were associated with a high tumor mutational burden and high microsatellite instability. SMARCA4 mutations were accompanied by KRAS, KEAP1, TP53 and STK11 mutations. No significant difference was observed in the immunotherapy response between patients with and without SMARCA4 mutations. When KRAS or STK11 mutations were present, immunotherapy effectiveness was poorer; however, when both SMARCA4 and TP53 mutations were present, immunotherapy was more effective. Furthermore, low SMARCA4 expression predicted a higher immunophenoscore, and SMARCA4 expression was correlated with certain immune microenvironment features. Taken together, our results suggest that SMARCA4 mutations and low expression might be associated with poor LUAD prognosis. Additionally, immunotherapy efficacy in patients with SMARCA4 mutations depended on the co‐mutant genes. Thus, SMARCA4 could be an important factor to be considered for LUAD diagnosis and treatment.

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SMARCA4 and SMARCE1 in gastric cancer: Correlation with ARID1A, and microsatellite stability, and SMARCE1/ERBB2 co‐amplification

et al. 2023

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Background: Recent studies have shown an association between certain subunits of the SWI/SNF complex with specific tumor characteristics in gastric cancer (GC). In an earlier study, we applied multiregional whole exome sequencing on multiple primary tumor samples and found alterations of the SWI/SNF complex in 78% of the cases. ERBB2, which encodes for Her2/neu, is a well-known predictive biomarker used to guide the treatment of GC in the palliative setting. SMARCE1, which encodes for a subunit of the SWI/SNF complex, is localized in close genetic proximity to ERBB2.Aim: As little is known about the significance of the SWI/SNF complex in GC biology and the potential relationship between ERBB2 and SMARCE1 upregulation, we examined the expression patterns of SMARCA4 and SMARCE1, two mutually exclusive catalytic ATPase subunits of the SWI/SNF complex, in a well characterized GC cohort. Materials and Methods:The expression of SMARCA4 and SMARCE1 was studied by immunohistochemistry in connection with clinicopathological patient characteristics in a cohort of 468 GCs. Digital droplet polymerase chain reaction was performed for amplification analysis on ERBB2 and SMARCE1.Results: Immunohistochemical staining of whole-mount tissue sections found a diffusely "gray scale" expression of SMARCA4 in 446 (95.2%) GCs and of SMARCE1 in 463 (98.8%) GCs. The expression of SMARCA4 and SMARCE1 correlated significantly with ARID1A, p53, and microsatellite status. No correlation was found with the patient prognosis. The amplification analysis of SMARCE1 showed amplification in 4 of 34 cases. In 3 of 34 cases, SMARCE1 was co-amplified with ERBB2. We also found a co-expression of SMARCE1 and Her2/neu in a subset of patients. Conclusion:While the effect of a co-amplification is currently unknown, synergistic effects of SMARCE1 and Her2/neu overexpression should be

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SMARCA4 and SMARCE1 in gastric cancer: Correlation with ARID1A, and microsatellite stability, and SMARCE1/ERBB2 co‐amplification

Cited by 5 publications

References 41 publications

SMARCA4 Mutations in Gastroesophageal Adenocarcinoma: An Observational Study via a Next-Generation Sequencing Panel

SMARCA4 Mutations in Gastroesophageal Adenocarcinoma: An Observational Study via a Next-Generation Sequencing Panel

SMARCA4 mutations and expression in lung adenocarcinoma: prognostic significance and impact on the immunotherapy response

SMARCA4 and SMARCE1 in gastric cancer: Correlation with ARID1A, and microsatellite stability, and SMARCE1/ERBB2 co‐amplification

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